Effect of flavopiridol on normal cells and tissues. (a) Histological section (10×) of the spleen of an untreated immunocompetent C57BL/6 mouse, showing a rich population of lymphocytes forming the germinal centers and marginal zone of the folliculi of the white pulp, surrounded by the blood-filled sinusoids of the red pulp. (b) Histological section (10×) of the spleen of an immunocompetent mouse 96 hours after initiation of treatment with daily IV bolus injection of flavopiridol, showing a marked depletion of lymphocytes, and only remnants of the white pulp. (c) Histological section of the thymus (10×) of a nontreated immunocompetent mouse showing the densely populated cortex by lymphocytes, surrounding the medullary areas of the lobules. (d) Histological section of a thymus (10×) of a flavopiridol-treated mouse showing an atrophic thymus, in which most lymphoid areas have disappeared. (e) ApopTag immunohistochemistry of the spleen (50×) of a nontreated mouse showing the rare presence of apoptotic brown-stained cells. (f) ApopTag immunohistochemistry of the spleen (50×) of a mouse 48 hours after initiation of treatment with flavopiridol, showing multiple brown-stained apoptotic lymphocytes in the follicular centers of the white pulp. (g) ApopTag immunostaining of the thymus (10×) of a nontreated immunocompetent mouse showing the lack of apoptosis in the lymphocyte-formed cortex. (h) ApopTag immunostaining of the thymus (10×) of a flavopiridol-treated mouse, showing a brown-stained, atrophic cortex caused by the death of thymocytes through apoptosis.